Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.5.7.1 (methylenetetrahydrofolate reductase)
 2,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Polymorphisms in genes can lead to differences in the level of susceptibility of individuals to potentially adverse effects of environmental influences, such as chemical exposure, on prenatal development or male or female reproductive function. We have reviewed the literature in this area, with the caveat that papers involving straight gene knock-outs in experimental animals, without a clear human relevance, were largely excluded. This review represents current knowledge in this rapidly moving field, presenting both human epidemiological and animal data, where available. Among the polymorphic genes and environmental interactions discussed with respect to prenatal development are those for P-glycoprotein (multidrug resistance protein) and the avermectins; methylenetetrahydrofolate reductase (MTHFR), an enzyme in folate metabolism, and dietary folic acid; transforming growth factor alpha (TGFalpha) and cigarette smoke; and alcohol dehydrogenase (ADH) and cytochrome P-450 (CYP) 2E1 in association with alcohol consumption. Effects on male reproduction attributable to gene-environment interaction involve infertility seen as a result of either organophosphorous (OP) pesticide interaction with the polymorphic paraoxonase (PON1) gene or antiandrogenic agent interaction with the androgen receptor (AR). MTHFR, folate metabolism, and dietary folic acid are also considered in conjunction with preeclampsia and early pregnancy loss, and the effect of the interaction of glutathione S-transferase (GST) with exposure to benzene or cigarette smoke on pregnancy maintenance is explored. As a conclusion, we offer a discussion of lessons learned and suggested research needs.
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PMID:Gene-environment interactions: a review of effects on reproduction and development. 1560 83

Our previous results indicated a moderate association between the methylenetetrahydrofolate reductase (MTHFR) gene 677C-T variant and an increased risk of non-syndromic cleft lip with or without cleft palate (nsCL/P) among the northern but not southern population in China, suggesting possible genetic heterogeneity in the etiology of nsCL/P between these two populations. It remains unknown whether the transforming growth factor alpha (TGFA) gene TaqI polymorphism and transforming growth factor beta 3 (TGFB3) gene CA repeats influence the risk of nsCL/P differently between the northern and southern Chinese populations. In this study of 188 Chinese case-parent triads, we found an independent association between the TGFB3 variant and risk of nsCL/P (OR = 2.10, 95% CI: 1.25-3.54 for heterozygotes; OR = 1.78, 95% CI: 0.83-3.83 for homozygotes). The MTHFR variant was associated with an increased risk of nsCL/P among children in the north (OR = 3.11, 95% CI: 1.18-8.23 for heterozygotes; OR = 3.36, 95%CI: 1.14-9.93 for homozygotes) and appear to interact marginally with the TGFB3 variant in the occurrence of nsCL/P among southern subjects (OR = 0.26, 95% CI: 0.06-1.07). No association was found between the TGFA variant and risk of nsCL/P in our data. Our results suggest that the TGFB3 gene variant may be an important genetic risk factor for nsCL/P occurrence in Chinese children, and we found no evidence of heterogeneity between northern and southern Chinese populations in the associations between TGFB3 and TGFA variants and risk of nsCL/P, but these results warrant further investigation.
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PMID:MTHFR, TGFB3, and TGFA polymorphisms and their association with the risk of non-syndromic cleft lip and cleft palate in China. 2008 68